Kingella kingae Spondylodiscitis: Treatment Failure With Flucloxacillin.

Kingella kingae infections generally respond well to most beta-lactam antibiotics. We investigated an antibiotic treatment failure in a 3-year-old with K. kingae L3-4 spondylodiscitis. Her disease progressed even after 19 days of high-dose intravenous flucloxacillin. The clinical isolate did not produce a beta-lactamase and despite phenotypic testing and whole-genome sequencing, the mechanism of flucloxacillin resistance remains unknown.

Osteoarticular Infections of the Chest Wall Due to Kingella Kingae: A Series of 8 Cases.

Osteoarticular infections of the chest wall are relatively uncommon in pediatric patients and affect primarily infants and toddlers. Clinical presentation is often vague and nonspecific. Laboratory findings may be unremarkable in osteoarticular chest wall infections and not suggestive of an osteoarticular infection. Causative microbes are frequently identified if specific nucleic acid amplification assays are carried out. In the young pediatric population, there is evidence that Kingella kingae is 1 of the main the main causative pathogens of osteoarticular infections of the chest wall.

Management of Pediatric Acute Hematogenous Osteomyelitis, Part I: Antimicrobial Stewardship Approach and Review of Therapies for Methicillin-Susceptible Staphylococcus aureus, Streptococcus pyogenes, and Kingella kingae.

Acute hematogenous osteomyelitis (AHO), often occurring in young children, is the most frequently diagnosed type of osteomyelitis in pediatric patients. Optimizing antibiotics is essential as delays to receipt of appropriate therapy can lead to chronic osteomyelitis, as well as impairments in bone growth and development. Antimicrobial stewardship programs (ASPs) are in a key position to help improve the care of patients with AHO as they contain a pharmacist with expertise in antibiotic drug selection, optimization of dosing, and microbiologic test review. A literature search of the MEDLINE database was conducted from initiation through January 2018. Articles selected for the review focus on pathogen identification, pharmacokinetics and pharmacodynamics, efficacy and safety in children, transition from intravenous to oral therapy, duration of treatment, and antimicrobial stewardship interventions. This review will highlight the potential roles ASPs can have in improving the management of AHO in pediatric patients. These roles include the creation of clinical pathways, improving testing algorithms, antibiotic choice and dosing, intravenous to oral transitions, duration of treatment, and therapy monitoring. Overall, patients are most effectively treated by focusing treatments on age, presentation, local sensitivities, and directed therapy with pathogen identification.

Antimicrobial susceptibility testing of Kingella kingae with broth microdilution and disk diffusion using EUCAST recommended media.

OBJECTIVES: Increasing use of improved culture techniques and sensitive nucleic acid amplification assays have resulted in recognition of Kingella kingae as an important cause of invasive infections in young children, especially in septic arthritis, osteomyelitis, bacteraemia, and endocarditis. In 2016, EUCAST established clinical MIC breakpoints for K. kingae (published in EUCAST Clinical Breakpoint Tables v 7.0, 2017). The present study was carried out to produce MIC-zone diameter correlations for K. kingae on an international collection of isolates, with the aim of suggesting zone diameter breakpoints corresponding to the clinical MIC breakpoints. METHODS: Antimicrobial susceptibility testing was performed for 18 clinically relevant agents on a collection of 159 clinical isolates of K. kingae. Broth microdilution MIC determination and disk diffusion were performed according to EUCAST recommendations for fastidious organisms. RESULTS: The correlation between MICs and zone diameters was good for all agents with EUCAST breakpoints for K. kingae. ß-lactamase was detected in 41 isolates (26%) and these isolates were resistant to aminopenicillins. These isolates were also resistant to trimethoprim-sulfamethoxazole. Resistance to tetracyclines was detected in 8% of all isolates. All resistant isolates were correctly categorized for these agents with the proposed zone diameter breakpoints. One isolate, resistant to erythromycin but susceptible to other macrolides, was categorized as susceptible with erythromycin disk diffusion. No resistance was detected for the cephalosporins, carbapenems, and fluoroquinolones tested. CONCLUSION: Based on the results in this study, zone diameter breakpoints for K. kingae calibrated to EUCAST clinical MIC breakpoints were proposed and approved by EUCAST.

Genome Analysis of Kingella kingae Strain KWG1 Reveals How a ß-Lactamase Gene Inserted in the Chromosome of This Species.

We describe the genome of a penicillinase-producing Kingella kingae strain (KWG1), the first to be isolated in continental Europe, whose bla(TEM-1) gene was, for the first time in this species, found to be chromosomally inserted. The bla(TEM) gene is located in an integrative and conjugative element (ICE) inserted in Met-tRNA and comprising genes that encode resistance to sulfonamides, streptomycin, and tetracycline. This ICE is homologous to resistance-conferring plasmids of K. kingae and other Gram-negative bacteria.

Kingella kingae: carriage, transmission, and disease.

Kingella kingae is a common etiology of pediatric bacteremia and the leading agent of osteomyelitis and septic arthritis in children aged 6 to 36 months. This Gram-negative bacterium is carried asymptomatically in the oropharynx and disseminates by close interpersonal contact. The colonized epithelium is the source of bloodstream invasion and dissemination to distant sites, and certain clones show significant association with bacteremia, osteoarthritis, or endocarditis. Kingella kingae produces an RTX (repeat-in-toxin) toxin with broad-spectrum cytotoxicity that probably facilitates mucosal colonization and persistence of the organism in the bloodstream and deep body tissues. With the exception of patients with endocardial involvement, children with K. kingae diseases often show only mild symptoms and signs, necessitating clinical acumen. The isolation of K. kingae on routine solid media is suboptimal, and detection of the bacterium is significantly improved by inoculating exudates into blood culture bottles and the use of PCR-based assays. The organism is generally susceptible to antibiotics that are administered to young patients with joint and bone infections. ß-Lactamase production is clonal, and the local prevalence of ß-lactamase-producing strains is variable. If adequately and promptly treated, invasive K. kingae infections with no endocardial involvement usually run a benign clinical course.

Prospective survey of acute osteoarticular infections in a French paediatric orthopedic surgery unit.

The epidemiology of acute paediatric osteoarticular infections (OAI) has recently evolved, mainly due to the improvement of microbiological diagnosis. We conducted a prospective study to analyse the recent epidemiology and the clinical evolution of paediatric OAI in order to validate the adequacy of our probabilistic first-line antibiotic treatment (intraveinous cefamandole + gentamicin). All children suspected of community acquired OAI were included and followed-up for 3 years. The etiologic diagnosis was based on blood cultures, joint aspirations and bone punctures. All osteoarticular (OA) samples were systematically inoculated into blood culture bottles. Real-time universal 16S rRNA and PCR targeted on Staphylococcus aureus, Kingella kingae, Streptococcus pneumoniae and Streptococcus pyogenes were performed twice a week. From 17 March 2007 to 26 February 2009, 98 septic arthritis, 70 osteomyelitis, 23 osteoarthritis and six spondylodiscitis were analysed. A portal of entry was suspected in 44% of cases, including 55% of otorhinolaryngological infections. C reactive protein was the most sensitive inflammatory marker. PCR increased by 54% the performance of bacteriological diagnosis. Among the patients completely investigated (blood culture and OAI samples), there were 63% documented OAI. The main pathogens found were K. kingae (52%), S. aureus (28%), S. pyogenes (7%), S. pneumoniae (3%) and Streptococcus agalactiae (2%). All isolated bacteria were sensitive to the probabilist treatment and outcome was favorable. PCR has significantly improved the performance and the delay of IOA diagnosis in children, for which K. kingae turned out to be the first causative agent. The probabilistic treatment was active against the main bacteria responsible for paediatric OAI.

Beta-lactamase production by Kingella kingae in Israel is clonal and common in carriage organisms but rare among invasive strains.

The purpose of this study was to investigate the prevalence of ß-lactamase and the genomic clonality of a large collection of Kingella kingae isolates from Israeli patients with a variety of invasive infections and asymptomatic pharyngeal carriers. ß-lactamase production was studied by the nitrocefin method and the minimum inhibitory concentrations (MICs) of penicillin and amoxicillin-clavulanate were determined by the epsilon (Etest) method. The genotypic clonality of isolates was investigated by pulsed-field electrophoresis (PFGE). ß-lactamase was found in 2 of 190 (1.1 %) invasive isolates and in 66 of 429 (15.4 %) randomly chosen carriage organisms (p < 0.001). Overall, 73 distinct PFGE clones were identified (33 among invasive organisms and 56 among carriage isolates). ß-lactamase production was found to be limited to four distinct PFGE clones, which were common among carriage strains but rare among invasive strains, and all organisms in the collection belonging to these four clones expressed ß-lactamase. The penicillin MIC of ß-lactamase-producing isolates ranged between 0.094 and 2 mcg/mL (MIC50: 0.25 mcg/mL; MIC90: 1.5 mcg/mL) and that of amoxicillin-clavulanate between 0.064 and 0.47 mcg/mL (MIC50: 0.125 mcg/mL; MIC90: 0.125 mcg/mL). The penicillin MIC of ß-lactamase non-producing isolates ranged between <0.002 and 0.064 mcg/mL (MIC50: 0.023 mcg/mL; MIC90: 0.047 mcg/mL). Although ß-lactamase production is prevalent among K. kingae organisms carried by healthy carriers, the low invasive potential of most colonizing clones results in infrequent detection of the enzyme in isolates from patients with clinical infections. The exceptional presence of ß-lactamase among invasive organisms correlates with the favorable response of K. kingae infections to the administration of ß-lactamase-susceptible antibiotics.

Simplifying the treatment of acute bacterial bone and joint infections in children.

The treatment of acute hematogenous bone and joint infections of children - osteomyelitis (OM), septic arthritis (SA) and OM-SA combination (OM+SA) - has simplified over the past years. The old approach included months-long antibiotic treatment, started intravenously for at least a week, followed by oral completion of the course. Recent prospective randomized trials show that most cases heal with a total course of 3 weeks (OM, OM+SA) or 2 weeks (SA) of an appropriate antibiotic, provided the clinical response is good and C-reactive protein level has normalized. If the prevalence of methicillin-resistant Staphylococcus aureus and Kingella kingae is low, clindamycin and a first-generation cephalosporin are safe, inexpensive and effective alternatives. They should be administered in large doses and four times a day. Clindamycin, vancomycin and expensive linezolid are options against methicillin-resistant Staphylococcus aureus. Extensive surgery beyond a diagnostic sample by aspiration is rarely needed in uncomplicated cases.

[Osteoarticular infections: therapeutic proposals of the Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP)]. / Infections ostéoarticulaires : propositions thérapeutiques du Groupe de Pathologie Infectieuse Pédiatrique (GPIP) de la Société Française de Pédiatrie.

The empiric choice of initial antibiotherapy in osteoarticular infections in infants and children must take into consideration the actual epidemiology of principal pathogens, their respective antibiotic sensitivity profile, their pharmacokinetic and pharmacodynamic properties and the results of efficacy clinical studies. After a review of recent data concerning these four major points, the Paediatric Infectious Diseases Group of the French Society of Paediatrics (GPIP) has proposed guidelines for initial recommended schemes of antimicrobial therapy in acute and non complicated osteoarticular infections in infants and children.

[Epidemiology and bacteriological diagnosis of paediatric acute osteoarticular infections]. / Epidémiologie et diagnostic bactériologique des infections ostéoarticulaires aiguës de l'enfant.

Acute paediatric osteo-articular infections require a fast and sensitive diagnosis allowing a treatment directed to the causative pathogen. Many micro-organisms can be incriminated, but Staphylococcus aureus and Kingella kingae markedly prevail. K. kingae became the first bacterial species responsible for septic arthritis in children < 3 years. More rarely, (2)haemolytic Streptococci and Streptococcus pneumoniae are found. The incidence of community acquired S. aureus resistant to oxacillin in osteo-articular infections is still low in France. The microbiological diagnosis of septic arthritis relies upon analysis of articular fluid, which requires systematic inoculation of a blood culture vial to increase the recovery rate of K. kingae. If the culture is negative, it is recommended to carry out a universal PCR or a PCR targeted to the main germs responsible for septic arthritis. Indeed, PCR represents an undeniable benefice for the diagnosis of paediatric septic arthritis, particularly for the DNA detection of K. kingae. The diagnosis of acute osteomyelitis relies primarily upon blood cultures, since the bone puncture is not a systematic procedure in this setting. Their efficiency is low, and there is still a need to look for other arguments of diagnosis such as search of possible portals of entry or specific serologies.

Kingella kingae infections of the skeletal system in children: diagnosis and therapy.

As the result of improved bacteriological techniques, Kingella kingae is emerging as an important cause of infections of the skeletal system in children younger than 2 years of age. This review details the bacteriological features and detection methods of this pathogen, as well as the epidemiology, clinical presentation, treatment and prognosis of septic arthritis, osteomyelitis and diskitis caused by the organism.

Antibiotic susceptibility of Kingella kingae isolates from respiratory carriers and patients with invasive infections.

The antimicrobial drug susceptibilities of 145 isolates of Kingella kingae to eight antibiotics were determined by the disc diffusion method. In addition, penicillin MICs were determined by the Etest. Study isolates included 37 from blood, 34 from the skeletal system and 74 from respiratory carriers. All isolates were beta-lactamase negative and susceptible to erythromycin, gentamicin, chloramphenicol, tetracycline and ciprofloxacin. A single isolate exhibited resistance to trimethoprim-sulphamethoxazole, and 56 (38.6%) were resistant to clindamycin. The penicillin MIC(50) was 0.023 mg/L and the MIC(90) was 0.047 mg/L. The distribution of MIC values did not differ according to the site of isolation.